Loreto C, Rapisarda V, Carnazza M L, Musumeci G, Valentino M, Fenga C, Martinez G
Department of Anatomy, Diagnostic Pathology, Forensic Medicine, Hygiene and Public Health, University of Catania, Catania, Italy.
Histol Histopathol. 2008 Mar;23(3):319-26. doi: 10.14670/HH-23.319.
We previously showed that apoptosis in the lungs of sheep exposed to fluoro-edenite fibres is induced via the receptor pathway. The present study was performed to gain further insights into the mechanisms of activation of programmed cell death induced by the fibres. Fluoro-edenite fibres are similar in size and morphology to some amphibolic asbestos fibres. They have been found in benmoreitic lavas, in the local stone quarry, in building materials and in road paving at Biancavilla, a town in eastern Sicily (Italy), where epidemiological surveys revealed a cluster of mortality from pleural mesothelioma. Inhalation of asbestos fibres can cause chronic inflammation and carcinogenesis. Since fluoro-edenite has been shown to activate the apoptotic process, we set out to characterise the expression of apoptosis-regulating proteins in fluoro-edenite-exposed lung disease and sought to determine if apoptosis results from fluoro-edenite exposure. Lung tissue from apparently healthy sheep habitually grazing near Biancavilla was processed for immunohistochemical localisation of bcl-2 and bax. Results showed epithelial and interstitial bax overexpression, especially in cells directly in contact with the fibres, and negative bcl-2 immunoexpression. TUNEL-positive cells were detected in alveoli and connective tissue. The integrity of alveolar epithelium and alveolar apoptosis are critical determinants in the pathways that initiate fibrogenesis in the lung and fibroblastic foci are usually found close to abnormal or denuded alveolar epithelium. Our results are consistent with the hypothesis that apoptosis is an important mechanism for removing cells with irreparable fluoro-edenite-induced genetic changes that predispose them to a neoplastic evolution.
我们之前表明，暴露于氟绿脱石纤维的绵羊肺部的细胞凋亡是通过受体途径诱导的。本研究旨在进一步深入了解由这些纤维诱导的程序性细胞死亡的激活机制。氟绿脱石纤维在大小和形态上与一些两性石棉纤维相似。它们已在意大利西西里岛东部城镇比安卡维拉的斑脱岩熔岩、当地采石场、建筑材料和道路铺设中被发现，在那里的流行病学调查显示了胸膜间皮瘤的死亡聚集现象。吸入石棉纤维可导致慢性炎症和致癌作用。由于已证明氟绿脱石能激活凋亡过程，我们着手表征氟绿脱石暴露所致肺部疾病中凋亡调节蛋白的表达，并试图确定细胞凋亡是否由氟绿脱石暴露引起。对在比安卡维拉附近习惯性放牧的看似健康的绵羊的肺组织进行处理，以进行bcl-2和bax的免疫组织化学定位。结果显示上皮和间质中bax过表达，尤其是在直接与纤维接触的细胞中，且bcl-2免疫表达呈阴性。在肺泡和结缔组织中检测到TUNEL阳性细胞。肺泡上皮的完整性和肺泡凋亡是启动肺部纤维生成途径的关键决定因素，并且通常在异常或剥脱的肺泡上皮附近发现成纤维细胞灶。我们的结果与以下假设一致，即细胞凋亡是清除具有氟绿脱石诱导的不可修复的基因变化的细胞的重要机制，这些基因变化使它们易于发生肿瘤演变。
